Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Survival analysis over a 20-year period of a Brazilian cohort of blood donors coinfected HIV-HCV

ABSTRACT Among individuals coinfected with HCV and HIV, studies of mortality from non-hepatic causes have shown inconsistent results. The aim of this study was to investigate the contribution of HCV and HIV co-infection to mortality from hepatic and non-hepatic causes in Brazil. This retrospective cohort study included blood donors from Fundação Pró-Sangue de São Paulo (FPS) who were followed from 1994 to 2016 to compare mortality and its causes between HIV-HCV coinfected individuals versus those seronegative for all tested infections. Records from the FPS database and the Mortality Information System were linked through a probabilistic record Relationship (RL). The Hazard Ratio (HR) was estimated using Cox multiple regression models. HCV-HIV coinfected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 14.54), non-liver neoplasms (HR = 2.55), infections (HR = 10.37) and liver disease (HR = 7.0). In addition, HCV mono-infected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 2.23), liver cancer (HR = 32.21), liver disease (HR = 14.92), infection (HR = 3.22), and trauma (HR = 1.68). Individuals coinfected with HCV and HIV have increased overall mortality and death due to infections, liver diseases and non-liver neoplasms as compared to those uninfected with HCV and HIV.

Validation of a formula predictive of peripheral blood stem cell yield and successful collection in healthy allogeneic donors

ABSTRACT Background: An efficient mobilization and collection of peripheral blood stem cells (PBSCs) are crucial to optimize engraftment in the recipient. We aim to validate a formula that predicted CD34+ cell yield and to describe variables that correlated with high yield mobilization and collection in healthy donors. Methods: We retrospectively analyzed clinical and laboratory data from healthy donors who underwent PBSC collection from 2006 to 2015. The predicted number of collected cells was calculated using the following formula: Total number of CD34+ (cells × 106/kg) yield = [(peripheral CD34+ cells/µL) × (0.43)/recipient body weight (kg)] × total liters processed. Results: We evaluated 338 collections from 307 allogeneic PBSC donors. The predicted versus the observed number of CD34+ cells/kg collected yielded an r-value of 0.775 (0.726-0.816; p < 0.0001). Overall, 55.7% donors had an acceptable mobilization level. Donors with a body weight <67 kg were less likely to yield a satisfactory CD34+ cell count (OR = 0.44; 95% CI 0.24-0.81), while a white blood cell (WBC) count >40 × 109/L (OR = 3.69; 2.11-6.46) and platelet count ≥200 × 109/L (OR = 2.09; 1.26-3.47) on the day of collection predicted a good level of mobilization. Predictors of a CD34+ cell yield/kg of ≥4 × 106 with only one apheresis session were: circulating CD34+ cells/µL >40 (OR = 16; 6.94-36.93), hemoglobin ≥14 g/dL (OR = 3.40; 1.53-7.57), WBC >40 × 109/L (OR = 4.61; 2.10-10.10) on the first collection day, and a positive delta weight between donor and recipient (OR = 3.10; 1.36-7.06). Conclusion: The formula for predicting CD34+ cell yield is accurate and suggests the optimal length of time for successful leukapheresis. Validation of the predictors of successful mobilization will help to further refine PBSC leukapheresis procedures.

Test seeking: are healthcare professionals referring people to blood centers for infections marker testing?

ABSTRACT Background: Test-seeking is associated with HIV in Brazilian blood donors. This study sought to investigate the frequency with which three different donor groups: deferred donors, accepted donors who tested HIV positive [HIV (+)], and accepted donors who tested infectious disease markers negative [IDM (−)], came to the blood bank at the suggestion of a health care professional. Study design and methods: Donors deferred for reporting high-risk behaviors and participants in an HIV risk factor case-control study completed a confidential audio computer-assisted self-interview (ACASI) that included two questions related to health care professionals and test-seeking. Results: Of 4013 enrolled deferred donors, 468 (11.8%) reported a health care professional suggested donation as a way to be tested for infection. Of 341 HIV (+) and 791 IDM (−) participants, 43 (12.6%) and 11 (1.4%), respectively, reported a health care professional suggested donation as a way to be tested for infection. Physicians were the most frequently reported source of referral: [(61.5% of deferred, 69.1% of HIV (+), and 9.1% of IDM (−) donors)]. Conclusion: HIV (+) donors and deferred donors were 10 times more likely to report test-seeking behavior by suggestion of health care professional than IDM (−) donors. If true, efforts should be made to educate health care professionals and blood donors on how to safeguard the blood supply, emphasizing that HIV testing should be done at volunteer testing centers rather than at the blood centers.

Hepatitis C among blood donors: cascade of care and predictors of loss to follow-up

ABSTRACT OBJECTIVE To investigate the HCV cascade of care and to identify the factors associated with loss or absence to follow-up of patients identified as infected with hepatitis C through blood donation. METHODS Blood donors from 1994 to 2012, identified with positive anti- HCV by enzyme immunoassay and immunoblot tests were invited to participate in the study, through letters or phone calls. Patients who agreed to participate were interviewed and their blood samples were collected for further testing. The following variables were investigated: demographic data, data on comorbidities and history concerning monitoring of hepatitis C. Multiple regression analysis by Poisson regression model was used to investigate the factors associated with non-referral for consultation or loss of follow-up. RESULTS Of the 2,952 HCV-infected blood donors, 22.8% agreed to participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian. Of the 676 participants, 39.7% did not receive proper follow-up or treatment after diagnosis: 45 patients referred not to be aware they were infected, 61 did not seek medical attention and 163 started a follow-up program, but were non-adherent. The main reasons for inadequate follow-up were not understanding the need for medical care (71%) and health care access difficulties (14%). The variables showing a significant association with inadequate follow-up after multiple regression analysis were male gender (PR = 1.40; 95%CI 1.15–1.71), age under or equal to 50 years (PR = 1.36; 95%CI 1.12–1.65) and non-Caucasians (PR = 1.53; 95%CI 1.27–1.84). CONCLUSIONS About 40.0% of patients did not receive appropriate follow-up. These data reinforce the need to establish strong links between primary care and reference centers and the need to improve access to specialists and treatments.

Health-related quality of life among blood donors with hepatitis B and hepatitis C: longitudinal study before and after diagnosis

Introduction: There is evidence that patients suffering from chronic hepatic diseases, including chronic hepatitis B and chronic hepatitis C, have a reduced health-related quality of life. The aim of this study was to evaluate the impact of the notification of test results for hepatitis B and hepatitis C on the quality of life of blood donors. Methods: Over a 29-month period, this study assessed the quality of life of 105 blood donors with positive serological screening tests for hepatitis B and hepatitis C and donors who presented false-positive test results. The Medical Outcome Study 36-Item Short Form Health Survey Questionnaire was applied at three time points: (1) when an additional blood sample was collected for confirmatory tests; (2) when donors were notified about their serological status; and (3) when donors, positive for hepatitis B and hepatitis C, started clinical follow- up. Quality of life scores for the confirmed hepatitis B and hepatitis C groups were compared to the false-positive control group. Results: The domains bodily pain, general health perception, social function, and mental health and the physical component improved significantly in donors with hepatitis C from Time Point 1 to Time Point 3. Health-related quality of life scores of donors diagnosed with hepatitis B and hepatitis C were significantly lower in six and four of the eight domains, respectively, compared to the false-positive control group. Conclusion: A decreased quality of life was detected before and after diagnosis in blood donors with hepatitis B and hepatitis C. Contrary to hepatitis B positive donors, the pos- sibility of medical care may have improved the quality of life among hepatitis C positive donors.

Phylogenetic analysis of the emergence of main hepatitis C virus subtypes in São Paulo, Brazil

ABSTRACTBACKGROUND: It is recognized that hepatitis C virus subtypes (1a, 1b, 2a, 2b, 2c and 3a) originated in Africa and Asia and spread worldwide exponentially during the Second World War (1940) through the transfusion of contaminated blood products, invasive medical and dental procedures, and intravenous drug use. The entry of hepatitis C virus subtypes into different regions occurred at distinct times, presenting exponential growth rates of larger or smaller spread. Our study estimated the growth and spread of the most prevalent subtypes currently circulating in São Paulo.METHODS:A total of 465 non-structural region 5B sequences of hepatitis C virus covering a 14-year time-span were used to reconstruct the population history and estimate the population dynamics and Time to Most Recent Common Ancestor of genotypes using the Bayesian Markov Chain Monte Carlo approach implemented in BEAST (Bayesian evolutionary analysis by sampling tree software/program).RESULTS:Evolutionary analysis demonstrated that the different hepatitis C virus subtypes had distinct growth patterns. The introduction of hepatitis C virus-1a and -3a were estimated to be circa 1979 and 1967, respectively, whereas hepatitis C virus-1b appears to have a more ancient entry, circa 1923. Hepatitis C virus-1b phylogenies suggest that different lineages circulate in São Paulo, and four well-supported groups (i.e., G1, G2, G3 and G4) were identified. Hepatitis C virus-1a presented the highest growth rate (r = 0.4), but its spread became less marked after the 2000s. Hepatitis C virus-3a grew exponentially until the 1990s and had an intermediate growth rate (r = 0.32). An evident exponential growth (r = 0.26) was found for hepatitis C virus-1b between 1980 and the mid-1990s.CONCLUSIONS:After an initial period of exponential growth, the expansion of the three main subtypes began to decrease. Hepatitis C virus-1b presented inflated genetic diversity, and its transmission may have been sustained by different generations and transmission routes other than blood transfusion. Hepatitis C virus-1a and -3a showed no group stratification, most likely due to their recent entry.

Risk factors for deferral due to low hematocrit and iron depletion among prospective blood donors in a Brazilian center

OBJECTIVE: Deferral of blood donors due to low hematocrit and iron depletion is commonly reported in blood banks worldwide. This study evaluated the risk factors for low hematocrit and iron depletion among prospective blood donors in a large Brazilian blood center.METHOD: A case-control study of 400 deferred donors due to low hematocrit and 456 eligible whole blood donors was conducted between 2009 and 2011. Participants were interviewed about selected risk factors for anemia, and additional laboratory tests, including serum ferritin, were performed. Bivariate and multivariate analyses were performed to assess the association between predictors and deferral due to low hematocrit in the studied population and iron depletion in women.RESULTS: Donors taking aspirins or iron supplementation, those who reported stomachache, black tarry stools or hematochezia, and women having more than one menstrual period/month were more likely to be deferred. Risk factors for iron depletion were repeat donation and being deferred at the hematocrit screening. Smoking and lack of menstruation were protective against iron depletion.CONCLUSION: This study found some unusual risk factors related to gastrointestinal losses that were associated with deferral of donors due to low hematocrit. Knowledge of the risk factors can help blood banks design algorithms to improve donor notification and referral.

A comprehensive protocol to evaluate the use of blood and its components in Latin America and the Caribbean / Un protocolo integral para evaluar el uso de la sangre y sus componentes en América Latina y el Caribe

Blood transfusion safety is a critical part of appropriate health care. Considering the limited information available on the use of blood and its components in Latin America and the Caribbean, the Grupo Cooperativo iberoamericano de Medicina Transfusional (Ibero-American Cooperative Group for Transfusion Medicine; GCIAMT), through its Research and International Affairs committees, carried out a project to develop a protocol that would facilitate the evaluation of blood usage at the country, jurisdiction, and institutional levels in varied country contexts. Experts in blood safety from the Pan American Health Organization (Washington, DC, United States), the University of São Paulo (São Paulo, Brazil), the Hemocentro of São Paulo (São Paulo, Brazil), and GCIAMT designed a 2-step comprehensive blood-use evaluation protocol: step 1 collects data from blood requests, and step 2, from medical charts. At a minimum, 1 000 analyzed requests are necessary; as such, study periods vary depending on the number of transfusion requests issued. An Internet-based application, the Modular Research System-Study Management System (MRS-SMS), houses the data and produces reports on how hospitals request blood, how blood is issued, who requires blood and blood components, and as an added benefit, how many blood units are wasted and what the real demand for blood is.

La seguridad de las transfusiones de sangre constituye una parte fundamental de una apropiada atención de salud. Teniendo en cuenta la limitada información disponible sobre el uso de la sangre y sus componentes en América Latina y el Caribe, el Grupo Cooperativo Iberoamericano de Medicina Transfusional (GCIAMT), mediante sus comités de Investigación y de Asuntos Internacionales, llevó a cabo un proyecto de elaboración de un protocolo que facilitara la evaluación del uso de la sangre a nivel de país, jurisdiccional e institucional, en diversos contextos de país. Expertos en seguridad de la sangre de la Organización Panamericana de la Salud (Washington, DC, Estados Unidos), la Universidad de São Paulo (São Paulo, Brasil), el Hemocentro de São Paulo (São Paulo, Brasil) y el GCIAMT diseñaron un protocolo integral de evaluación del uso de la sangre en 2 etapas: en la primera se recopilan datos de las solicitudes de sangre, y en la segunda, de las historias clínicas. Como mínimo, es preciso analizar 1 000 solicitudes; por ello, los períodos de estudio varían en dependencia del número de solicitudes de transfusión expedidas. Una aplicación basada en internet, el Modular Research System, Study Management System, alberga los datos y elabora informes sobre cómo solicitan sangre los hospitales, cómo se expide la sangre, quién requiere sangre y componentes sanguíneos y, como beneficio añadido, cuántas unidades de sangre se desperdician y cuál es la demanda real de sangre.

Contribution of the Retrovirus Epidemiology Donor Study (REDS) to research on blood transfusion safety in Brazil

The Retrovirus Epidemiology Donor Study (REDS) program was established in the United States in 1989 with the purpose of increasing blood transfusion safety in the context of the HIV/AIDS and human T-lymphotropic virus epidemics. REDS and its successor, REDS-II were at first conducted in the US, then expanded in 2006 to include international partnerships with Brazil and China. In 2011, a third wave of REDS renamed the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) was launched. This seven-year research program focuses on both blood banking and transfusion medicine research in the United States of America, Brazil, China, and South Africa. The main goal of the international programs is to reduce and prevent the transmission of HIV/AIDS and other known and emerging infectious agents through transfusion, and to address research questions aimed at understanding global issues related to the availability of safe blood. This article describes the contribution of REDS-II to transfusion safety in Brazil. Articles published from 2010 to 2013 are summarized, including database analyses to characterize blood donors, deferral rates, and prevalence, incidence and residual risk of the main blood-borne infections. Specific studies were developed to understand donor motivation, the impact of the deferral questions, risk factors and molecular surveillance among HIV-positive donors, and the natural history of Chagas disease. The purpose of this review is to disseminate the acquired knowledge and briefly summarize the findings of the REDS-II studies conducted in Brazil as well as to introduce the scope of the REDS-III program that is now in progress and will continue through 2018.

Temporal distribution of blood donations in three Brazilian blood centers and its repercussion on the blood supply

BACKGROUND:Seasonal distribution of blood donation hinders efforts to provide a safe and adequate blood supply leading to chronic and persistent shortages. This study examined whether holidays, geographical area and donation type (community versus replacement) has any impact on the fluctuation of donations. METHODS: The numbers of blood donations from 2007 through 2010 in three Brazilian Retrovirus Epidemiological Donor Study II (REDS-II) participating centers were analyzed according to the week of donation. The weeks were classified as holiday or non-holiday. To compare donations performed during holiday versus non-holiday weeks, tabulations and descriptive statistics for weekly donations by blood center were examined and time series analysis was conducted. RESULTS: The average weekly number of donations varied according to the blood center and type of week. The average number of donations decreased significantly during Carnival and Christmas and increased during the Brazilian National Donor Week. The fluctuation was more pronounced in Recife and Belo Horizonte when compared to São Paulo and higher among community donors. CONCLUSION: National bank holidays affect the blood supply by reducing available blood donations. Blood banks should take into account these oscillations in order to plan local campaigns, aiming at maintaining the blood supply at acceptable levels. .

Púrpura trombocitopênica trombótica: remissão completa em paciente com mau prognóstico após tratamento com plasmaférese terapêutica e rituximabe / Successful outcome in poor-prognostic acute thrombotic thrombocytopenic purpura treated with plasma exchange and rituximab

A púrpura trombocitopênica trombótica (PTT) é uma doença rara e fatal que deve ser diagnosticada e tratada prontamente a fim de se obter melhor resposta terapêutica. Apresentamos um caso de PTT aguda grave tratada com plasmaférese e rituximabe. Ao diagnóstico, a paciente apresentava anemia hemolítica microangiopática, icterícia, febre, convulsões, seguidas por coma e choque hipovolêmico. Os exames laboratoriais iniciais mostravam DHL=2.860 IU/L, contagem de plaquetas de 37 x 10(9)/L, hemoglobina de 5,1 g/dL e no esfregaço de sangue periférico havia a presença de esquizócitos. Iniciado tratamento para PTT com pulsoterapia com metilprednisolona e plasmaféreses terapêuticas diárias com troca de uma volemia plasmática e substituição com plasma fresco congelado. Após cinco sessões de plasmaférese, houve piora no quadro neurológico, acompanhado por aumento importante de DHL, ALT, AST e a contagem de plaquetas era de 72 x 10(9)/L. Iniciamos o uso de rituximabe na dose padrão de 375mg/m²/semana/4 semanas e passamos a utilizar plasma pobre em crioprecipitado como reposição durante as plasmaféreses. Dois dias após a mudança na conduta terapêutica, houve importante melhora do quadro neurológico, estabilização da contagem de plaquetas e queda acentuada de DHL. Após 23 procedimentos de plasmaférese e quatro doses de rituximabe, a paciente apresentou remissão completa, mantida há 34 meses. A plasmaférese terapêutica com plasma pobre em crioprecipitado e o uso concomitante de rituximabe foi uma estratégia útil no tratamento deste caso de PTT aguda grave. Porém, ensaios clínicos prospectivos e randomizados são necessários para confirmar estes achados.

Thrombotic thrombocytopenic purpura (TTP) is a rare severe disease that must be diagnosed and treated promptly for a successful outcome. We report a case of severe acute TTP treated with plasma exchange and rituximab. The patient presented at diagnosis with severe microangiopathic haemolytic anemia, jaundice, fever, seizures followed by coma and hypovolemic shock. Her LDH was 2,860 IU/L; platelet count 37 x 10(9)/L; hemoglobin 5.1 g/dL; blood smears contained schistocytes. Treatment for TTP was started with pulses of methylprednisolene and daily single-volume plasma exchange using fresh frozen plasma. After five plasma exchanges, the neurological status worsened, LDH increased sharply as did ALT and AST and the platelet count dropped to 72 x 10(9)/L. Rituximab (weekly doses of 375 mg/m² for 4 weeks) and plasma exchange with cryosupernatant substitution fluid were initiated. Within two days there was neurological improvement, stable platelet levels and decreased LDH. Complete remission, achieved after 23 plasma exchanges and four doses of rituximab, has been maintained for 34 months. Plasma exchange with cryosupernatant substitution fluid and rituximab played an important role in the successful treatment of this patient with severe acute TTP. A systematic clinical trial should be considered in order to confirm these findings.

Perfil epidemiológico de doadores de sangue com diagnóstico sorológico de sífilis e HIV / Epidemiological profile of blood donors with serologic diagnosis of syphilis and HIV

O perfil dos doadores de sangue com diagnóstico sorológico de sífilis e HIV foi avaliado através de um estudo transversal e um estudo caso-controle. Fatores de risco para HIV que deveriam ter gerado a recusa dos doadores foram relatados por 48,9 por cento dos casos. O principal preditor de infecção pelo HIV foi homem que mantém/manteve relação sexual com outro homem. Doadores de sangue com sífilis pregressa eram mais velhos, vinculados e parte referiu estilo de vida de risco no passado. Os com sífilis recente eram mais jovens, altruístas, apresentaram mais relatos de orientação homo ou bissexual e maior associação com o HIV do que aqueles com sífilis pregressa. O perfil de doadores de sangue com sorologias alteradas é útil para direcionar as políticas de sangue e critérios de triagens clínicas e sorológicas dos hemocentros.

The profile of blood donors with serologic diagnosis of syphilis na HIV was studied in a cross-sectional study and a case-control study. Risk factors used as donor deferral criteria were reported by 48.9 per cent of cases. Male-male sex was the strongest predictor of HIV infection. Donors with past syphilis were more likely to be older, replacement donors and part of them referred past of high risk behavior. Donors with recent syphilis were younger, the majority of them community donors, referred male-male sex more frequently and presented a higher association with HIV when compared to those with past disease. The study of the epidemiological profile of seropositive blood donors is useful to improve blood banks pre-donation and serologic screenings and guide blood safety policies.

Significance of isolated hepatitis B core antibody in blood donors from Säo Paulo

The clinical significance of isolated anti-HBc is still a challenge. To elucidate the real importance of this finding in our blood donors, an investigation algorithm was tested. One hundred and twelve isolated anti-HBc seropositive blood donors underwent clinical evaluation and retesting of HBV markers. Those who presented repeatedly reactive isolated anti-HBc, received a single dose of hepatitis B recombinant vaccine to verify anti-HBs early response. A HBV-DNA determination by PCR was done for those who did not test positive to anti-HBs after vaccine. The level of anti-HBc was recorded as a ratio of the sample-to-cut-off values (S:C ratio) in 57 candidates at donation. Comparing true and false-positive anti-HBc results, the different S:C ratios of them were statistically significant and when less than 2, implying in a false-positive result probability over 80 percent. A high percent of false-positive results (16.07 percent) was verified after anti-HBc retesting. HBV immunity was characterized in 49.11 percent, either by anti-HBs detection in retesting (15.18 percent), or after a single dose HBV vaccination (33.93 percent). HBV-DNA was negative in all tested donors. In conclusion, this algorithm was useful to clarify the meaning of isolated anti-HBc in most of our blood donors